Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 11 children (mean age 44.2 months) with symptoms suggesting upper intestinal dysfunction (nonulcer dyspepsia), in nine children (mean age 27.3 months) with gastroesophageal reflux (GER) disease, and in seven controls (mean age 20.4 months) we investigated fasting [for 3 hr or until two migrating motor complexes (MMC) were observed] and fed (90 min) antroduodenal motility by means of perfused catheter system; furthermore, we measured both gastric emptying of a radiolabeled milk formula and fasting duodenogastric reflux during manometry by assessing bile salt concentration in gastric aspirates. No structural abnormalities of gastrointestinal tract and organic disorders were detected in the patients. In a high proportion of both groups of patients we found manometric abnormalities of interdigestive and fed motor patterns that were not seen in the controls: absence of antral phase III of MMC; significant decrease of antral and/or duodenal motor activity during fasting and/or fed periods; abnormal propagation or configuration of MMC phase III that was significantly shorter than in controls; bursts of sustained fasting and/or fed phasic duodenal activity, frequently uncoordinated with adjacent gut segments. When compared to controls, the mean intragastric concentration of bile salts during all MMC phases and the mean 1-hr percent gastric activity of the radiolabeled milk were significantly higher in the two groups of patients. We conclude that in a high proportion of children with nonulcer dyspepsia and of children with GER disease, gastrointestinal manometry may reveal significant irregularities of antral and duodenal motility, which are associated with increased duodenogastric reflux and delayed gastric emptying.
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PMID:Abnormalities of gastrointestinal motility in children with nonulcer dyspepsia and in children with gastroesophageal reflux disease. 186 98

Oesophageal injury secondary to gastro-oesophageal reflux is unlikely to be due to the effects of hydrochloric acid alone. The present authors have investigated the development of acid and bile salt-induced oesophageal mucosal injury in a rabbit model. Solutions of hydrochloric acid and sodium taurocholate (ST) were perfused through an isolated oesophageal preparation and mucosal injury was determined by measuring the rate of H+ disappearance. Perfusion with acid alone in concentrations up to 10 mmol/l did not affect the H+ disappearance rate. Addition of 1 mmol/l ST to an acid perfusate resulted in loss of H+ from the system. The increase in H+ disappearance rate was associated with loss of ST from the perfusate. Sodium taurocholate was only lost from the system when in an acid medium. Increased rate of H+ disappearance occurred even after the bile salt had been washed out of the perfused oesophagus. The mechanism of bile salt-induced mucosal injury was unlikely to be due to mucosal disruption secondary to micelle formation since the critical micellar concentration of taurocholate was found to be greater than that used in the perfusate. These findings indicate that bile salts may be an important factor in hydrochloric acid-related damage to oesophageal mucosa, by acting through mechanisms unrelated to micelle formation.
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PMID:Bile salt-induced injury of rabbit oesophageal mucosa measured by hydrogen ion disappearance. 303 65

Gastroesophageal reflux is a common event during infancy. Developmental factors may be responsible for incompetence of the lower esophageal sphincter (LES) in this age group. We used the cat as a model to evaluate in vivo and in vitro the mechanical factors responsible for LES pressure during infancy. We found that in vivo the kitten develops lower LES pressure than the adult cat. For in vitro studies consecutive rings 1.75 mm wide were obtained from the LES region of 3-day-, 1-wk-, 3-wk-, and 6-wk-old kittens and of adult animals. Force-length curves were obtained in standard Tyrode's solution, in Tyrode's solution with high KCl, and in calcium-free Tyrode's solution with ethylenediaminetetraacetic acid disodium salt to determine basal, total, and passive forces, respectively. Active force is given by the difference between total and passive force. The maximum active force generated was lowest in the 3-day-old kittens and increased with age, being highest in the adult cat. Stresses, obtained by normalizing forces for the amount of muscle available, were greater in the kitten than the adult. The ratio of muscle thickness to its inner radius is markedly reduced in the kitten. As intraluminal or LES pressure is given by the product of stress and thickness-to-radius ratio, this might explain why lower pressures are generated despite the higher stresses developed.
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PMID:Developmental characteristics of the lower esophageal sphincter in the kitten. 402 56

Antacids are commonly used self-prescribed medications. They consist of calcium carbonate and magnesium and aluminum salts in various compounds or combinations. The effect of antacids on the stomach is due to partial neutralisation of gastric hydrochloric acid and inhibition of the proteolytic enzyme, pepsin. Each cation salt has its own pharmacological characteristics that are important for determination of which product can be used for certain indications. Antacids have been used for duodenal and gastric ulcers, stress gastritis, gastro-oesophageal reflux disease, pancreatic insufficiency, non-ulcer dyspepsia, bile acid mediated diarrhoea, biliary reflux, constipation, osteoporosis, urinary alkalinisation and chronic renal failure as a dietary phosphate binder. The development of histamine H2-receptor antagonists and proton pump inhibitors has significantly reduced usage for duodenal and gastric ulcers and gastro-oesophageal reflux disease. However, antacids can still be useful for stress gastritis and non-ulcer dyspepsia. The recent release of proprietary H2 antagonists has likely further reduced antacid use for non-ulcer dyspepsia. Other indications are still valid but represent minor uses. Antacid drug interactions are well noted, but can be avoided by rescheduling medication administration times. This can be inconvenient and discourage compliance with other medications. All antacids can produce drug interactions by changing gastric pH, thus altering drug dissolution of dosage forms, reduction of gastric acid hydrolysis of drugs, or alter drug elimination by changing urinary pH. Most antacids, except sodium bicarbonate, may decrease drug absorption by adsorption or chelation of other drugs. Most adverse effects from antacids are minor with periodic use of small amounts. However, when large doses are taken for long periods of time, significant adverse effects may occur especially patients with underlying diseases such as chronic renal failure. These adverse effects can be reduced by monitoring of electrolyte status and avoiding aluminum-containing antacids to bind dietary phosphate in chronic renal failure. Antacids, although effective for discussed indications of duodenal and gastric ulcer and gastro-oesophageal reflux disease, have been replaced by newer, more effective agents that are more palatable to patients. Antacids are likely to continue to be used for non-ulcer dyspepsia, minor episodes of heartburn (gastro-oesophageal reflux disease) and other clear indications. Although their wide-spread use may decline, these drugs will still be used, and clinicians should be aware of their potential drug interactions and adverse effects.
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PMID:Antacids revisited: a review of their clinical pharmacology and recommended therapeutic use. 1040 Apr 1

A collagen-like peptide with the sequence (GER)(15) GPCCG was synthesized to study the formation of a triple helix in the absence of proline residues. This peptide can form a triple helix at acidic and basic pH, but is insoluble around neutral pH. The formation of a triple helix can be used to covalently oxidize the cysteine residues into a disulfide knot. Three disulfide bonds are formed between the three chains as has been found at the carboxyl-terminal end of the type III collagen triple helix. This is a new method to covalently link collagen-like peptides with a stereochemistry that occurs in nature. The peptide undergoes a reversible, cooperative triple helix coil transition with a transition midpoint (T(m)) of 17 to 20 degrees C at acidic pH and 32 to 37 degrees C at basic pH. At acidic pH there was little influence of the T(m) on the salt concentration of the buffer. At basic pH increasing the salt concentration reduced the T(m) to values comparable to the stability at acidic pH. These experiments show that the tripeptide unit GER which occurs frequently in collagen sequences can form a triple helical structure in the absence of more typical collagen-like tripeptide units and that charge-charge interactions play a role in the stabilization of the triple helix of this peptide.
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PMID:The collagen-like peptide (GER)15GPCCG forms pH-dependent covalently linked triple helical trimers. 1079 37

Barrett's oesophagus is an acquired precancerous condition that develops from mucosal injury incurred due to chronic gastro-oesophageal reflux. The aim of this study was to determine if bile and/or acid components of the refluxate can induce DNA damage in vitro. The oesophageal cell lines FLO-1 and HET1-A were exposed to primary bile salts, individually or as a mixture, and the secondary bile salt sodium deoxycholate, in neutral or acidified media. Cells were then examined in the comet assay to measure DNA strand breaks. Cell viability was also monitored. Acidified media induced DNA damage in a pH- and time-dependent manner. The primary bile compounds sodium glycocholate, glycocholic acid, sodium taurocholate and taurochenodeoxycholate, as an equimolar mixture (100 microM), caused a small but significant (P < 0.028) elevation in DNA damage, but only at neutral pH in FLO-1 cells. Sodium deoxycholate (100 microM) caused a significant (P < 0.008) elevation in DNA damage in both cell lines, but again only at neutral pH. These data suggest that specific components of gastro-oesophageal refluxate are capable of causing DNA damage and may participate in the genesis and progression of Barrett's oesophagus via this mechanism.
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PMID:Acid and bile salts induce DNA damage in human oesophageal cell lines. 1521 32

This work describes a laboratory experiment intended to study the formation and spectral reflectance properties of stratified salt crusts that cause severe environmental degradations to soil and water resources in arid regions. Salt crusts were prepared by evaporating three types of saline solutions consisting of i) NaCl - Na2SO4, ii) Na2SO4 - MgSO4, and iii) NaCl - MgSO4 at an initial concentrations of 50 mmol L(-1). They were examined for evaporite mineralogy using X-ray diffraction, optical and reflected microscopes, and for spectral reflectance with a high-resolution spectroradiometer (GER 3700) in the visible and near-infrared regions (400-2500 nm). The study documented chemical and environmental implications of the spectral properties of salt formed from the studied saline-systems. The reported results can be used to understand remotely sensed signatures of salt crusts and their implications.
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PMID:Chemical and environmental implications of visible and near-infrared spectral features of salt crusts formed from different brines. 1524 96

Premalignant esophagogastric (EG) lesions develop against a background of chronic inflammation, called a premalignant condition. For esophageal squamous cell cancer, causal factors include alcohol, tobacco, hot beverages, oral consumption of opioids, and probably infectious agents. For adenocarcinoma in the Barrett's esophagus (BE), gastroesophageal reflux disease (GERD) is the principal causal factor. At the EG junction, adenocarcinoma arises either from the esophagus or from the proximal stomach (cardia). In the distal stomach, chronic gastritis with atrophy is the premalignant condition related to Helicobacter pylori infection. A high intake of salt and low intake of antioxidants also play a role. The histopathology of EG premalignant lesions is now included in the groups low-grade and high-grade intraepithelial neoplasia (IEN) of the revised Vienna classification. Endoscopy is the gold standard for detection of the lesions at the preclinical stage and their appearance is described in subtypes of the type 0 of the Japanese classification, with a distinction between protruding and nonprotruding lesions. There is a priority for primary prevention of causal factors rather than for mass screening, which is justified only in Japan for the prevention of stomach cancer. The trend to early detection of premalignant lesions justifies the development of mini-invasive endoscopic procedures of treatment.
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PMID:Premalignant lesions of the esophagogastric mucosa. 1529 42

The dramatic success of pharmacological acid suppression in healing peptic ulcers and managing patients with gastroesophageal reflux disease (GERD) has been reflected in the virtual abolition of elective surgery for ulcer disease, a reduction in nonsteroidal anti-inflammatory drug (NSAID)-associated gastropathy and the decision by most patients with reflux symptoms to continue medical therapy rather than undergo surgical intervention. However, a number of challenges remain in the management of acid-related disorders. These include management of patients with gastroesophageal symptoms who do not respond adequately to proton pump inhibitor (PPI) therapy, treatment of patients with nonvariceal upper gastrointestinal bleeding, prevention of stress-related mucosal bleeding, optimal treatment and prevention of NSAID-related gastrointestinal injury, and optimal combination of antisecretory and antibiotic therapy for the eradication of Helicobacter pylori infection. A number of new drugs are currently being investigated to provide a significant advance on current treatments. Some of them (namely potassium-competitive acid blockers (P-CABs) and CCK2-receptor antagonists) have already reached clinical testing while some others (like the antigastrin vaccine, H3-receptor ligands or gastrin-releasing peptide receptor antagonists) are still in preclinical development and need the proof of concept in human beings. Of the current approaches to reduce acid secretion, P-CABs and CCK2-receptor antagonists hold the greatest promise, with several compounds already in clinical trials. Although the quick onset of action of P-CABs (i.e. a full effect from the first dose) is appealing, the results of phase II studies with one such agent (namely AZD0865) did not show any advantages over esomeprazole. Thanks to their limited efficacy and the development of tolerance it is unlikely that CCK2 antagonists will be used alone as antisecretory compounds but, rather, their combination with PPIs will be attempted with the aim of reducing the long-term consequences of hypergastrinemia. While H2-receptor antagonists (especially soluble or over-the-counter formulations) will become the 'antacids of the third millennium' and will be particularly useful for on-demand symptom relief, clinicians will continue to rely on PPIs to control acid secretion in GERD and other acid-related diseases. In this connection, several new PPI formulations have been developed and two novel drugs (namely ilaprazole and tenatoprazole) are being studied in humans. The recently introduced immediate-release (IR) omeprazole formulation (currently available only in the USA) quickly increases intragastric pH and, given at bedtime, seems to achieve a better control of nocturnal acidity. IR formulations of other PPIs (including the investigational ones) will probably be available in the future and will enlarge our therapeutic armamentarium. Amongst the novel PPIs, tenatoprazole appears to be a true advance in the acid suppression therapy. Its long half-life (the longest among the available compounds) and longer duration of antisecretory action, with no difference between day and night, will allow the drug to go beyond the intrinsic limitations of currently available PPIs. Thanks to its favorable pharmacokinetics, the sodium salt of S-tenatoprazole is being developed and the preliminary results indicate that this drug has the potential to address unmet clinical needs. Although some decades have elapsed since the introduction of effective and safe antisecretory drugs in clinical practice and their use has stood the test of time, the ongoing research will further provide the clinician with more effective means of controlling acid secretion.
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PMID:Acid suppression therapy: where do we go from here? 1669 62

p63 is a member of the p53 protein family that regulates differentiation and morphogenesis in epithelial tissues and is required for the formation of squamous epithelia. Barrett's mucosa is a glandular metaplasia of the squamous epithelium that develops in the lower esophagus in the context of chronic, gastroesophageal reflux and is considered as a precursor for adenocarcinoma. Normal or squamous cancer esophageal cells were exposed to deoxycholic acid (DCA, 50, 100, or 200 microM) and chenodeoxycholic and taurochenodeoxycholic acid at pH 5. p63 and cyclooxygenase-2 (COX-2) expressions were studied by Western blot and RT-PCR. DCA exposure at pH 5 led to a spectacular decrease in the levels of all isoforms of the p63 proteins. This decrease was observed within minutes of exposure, with a synergistic effect between DCA and acid. Within the same time frame, levels of p63 mRNA were relatively unaffected, whereas levels of COX-2, a marker of stress responses often induced in Barrett's mucosa, were increased. Similar results were obtained with chenodeoxycholic acid but not its taurine conjugate at pH 5. Proteasome inhibition by lactacystin or MG-132 partially blocked the decrease in p63, suggesting a posttranslational degradation mechanism. These results show that combined exposure to bile salt and acid downregulates a critical regulator of squamous differentiation, providing a mechanism to explain the replacement of squamous epithelium by a glandular metaplasia upon exposure of the lower esophagus to gastric reflux.
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PMID:Downregulation of p63 upon exposure to bile salts and acid in normal and cancer esophageal cells in culture. 1761 80


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